Gene Editing Introduced to the Farming Industry

The last 20 years has seen a great advancement in the field of genetics, as we begin to unravel the mysteries of the genome.

This month US company Recombinetics managed to edit the genomes of individual dairy cows, causing the loss of their ability to grow horns. The company was approached by farmers to improve the quality of life for the cattle (and probably the odd irritating farmer that gets too close). 
Usually the horns of dairy cows would be removed after birth, leaving large scars and often painful bruising. In the past farmers have bred hornless cows with horned cattle to mask the horned gene, but this form of selective breeding has hindered herds with the absence of many desired traits. This process of gene editing has been hailed as a major milestone in the introduction of genetic modification in the farming industry.

Gene editing is significantly different from standard genetic modification. Whilst the latter adds foreign genes or bundles of nucleotides into a genome to "transform" the organism, gene editing makes tiny tweaks - minuscule even on a genetic level - to knock out or express genes of interest. Because this technique doesn't introduce any foreign DNA, the organism isn't deemed to be a conventional GMO (Genetically Modified Organism). Taking into consideration the general mood of GMOs right now however, farmers may have to shy away from these untraditional methods for the time being. Only at the beginning of this month Scotland had made claims to formally ban all GM crops once new EU powers come into place next year.

As most farmers acknowledge themselves, the use of GMOs is becoming a necessity due to the rising level of quality produce demanded by the consumer.
GM animals is understandably significantly different scientifically and ethically, but the abundant benefits of gene editing are starting to become widely apparent. Recombinetics are now looking to tweak the DNA of other cattle breeds to tolerate harsher environments, particularly warmer and more humid climates. If they succeed, many countries with typically inapt environments would be able to access a suitable, high quality breed of cattle to boost their economies.

What do you think about GMOs and gene editing? Do you think that we should advance into the field of commerical GM animals, withdraw from genetically manipulated produce altogether, or maybe focus on another method of providing sufficient benefit in the industry, for both farmer and consumer?

Leave a comment below!



Images retrieved from http://cdn.images.express.co.uk/img/dynamic/1/590x/cow-395509.jpg
 and http://www.farmersweekly.co.za/img/fwa201366134312.jpg

Why We Can't Live Forever

The average life expectancy of the typical human living 100 years ago was 31 years. Since the last century most of us now have a projected life expectancy of just over double that of a person living in the 1900s. The 2010 world average life expectancy at birth is 67.2 years (Provided by the CIA, see reference below), but still we cling to the prospect of extending our lives to live out further into older age. As well as different healthy lifestyle plans, guides to happiness and the abundance of medical care, the turn of the millennium has seen a rise in claims of "Miracle pills" that promise to extend life up to several decades, or even slow the ageing process itself. Pseudoscience or a breakthrough in modern medicine, it is an important field of science that illustrates the often conflicting nature of research. This article aims to outline the reasons why it is so hard for any living thing to biologically lengthen the duration of their lifespan.
3 "causes", or signals, of ageing stand out above the rest. They are as follows:

Telomere Shortening

The chromosomes in our genome carry all of the genes needed for an individual. Humans have 46 arranged into 23 pairs, which are replicated when a cell divides. An enzyme called DNA polymerase (DNA Pol) is needed to replicate the DNA in chromosomes during this process. DNA Pol enzyme has evolved over time to be very efficient at it's job, although one major drawback is that the enzyme falls off, just short of the end of every strand it uses to copy. In effect, the daughter strand produced is shorter than the original piece of DNA which arises concern, as the strand could now be missing important pieces of genetic material not copied across. Luckily organisms have adapted to combat this by protecting their chromosomes with telomeres - long repeats of Thymine and Adenine bases which "coat" the tips of the chromatids. The addition of telomeres at the end of DNA sequences protect coding DNA near the ends, so now where DNA Pol now falls off (in the telomere region) it erases a few codons of essentially otherwise useless fragments of TA repeats.
The human foetus synthesises/lengthens telomeres using Telomerase, an enzyme not normally found in the body after birth. As telomeres aren't replaced or lengthened over time once born, countless cell replication cycles shorten telomere regions over time until they disappear altogether. At that point, any genetic material located at the ends of chromosomes that was before protected would now be directly in the "firing line" of deletion. The absence of telomeres in old age has been linked with dementia as important cognitive genes have been erased during cell replication. Some cells are clever enough to notice when telomeres become a dangerously short length, but destroy their selves in order to prevent gene damage.
The shortening of telomeres cannot be stopped as an individual ages, except with the help of telomerase. Mice genetically modified to possess telomerase have been shown to reverse the signs of their own ageing in several studies. However, the addition of telomerase in somatic/adult human cells causes cancer.

Oxidative Stress

The mitochondria in our cells act like power stations, producing energy for our metabolism, growth and repair. Contrastingly, the process in which these organelles produce energy can actually damage cells in the long term.

Mitochondria are very similar to watermills - they produce a gradient (of protons taken from hydrogen, instead of water current) that is released and channelled through certain structures from one side of a membrane to another. These structures act like rotors, just like the wheel of a watermill, turning to create energy in the form of ATP. At the end of the line mitochondria are left with a handful of electrons that caused the gradient in the first place, so oxygen absorbs these to prevent any reactive species in the environment (reduction). However, often some oxygen atoms are reduced insufficiently causing Reactive Oxygen Species known as Free Radicals. Their reactivity can cause a lot of damage to cell membranes, proteins and even genetic material.
Over time a build up of free radicals has the potential to exert a large quantity of damage to tissue in the body. The build up of free radicals is called Oxidative Stress, and gets larger and more concentrated as an individual ages. Mitochondria can never stop producing energy or the cell will die, which means that free radicals will always be produced. 

There are specific enzymes that regulate these reactive species in the human body, and Vitamins E and C play a role in inhibiting free radicals from reacting with fat and genetic material. However the build-up of oxidative stress over time overtakes the regulatory catalysis of free radicals.

Human Evolution

Organisms live for different amounts of time before they begin to age; oak trees can endure centuries before they start to wither, whereas mice only live for a few years. It was previously thought that the size of an organism positively correlated to it's age but many examples in life have quashed this theory (e.g. smaller breeds of dog nearly always live longer than larger breeds, the same goes with humans too).

Evolution has caused species to live out longer or shorter lives for the reasons of reproduction. The whole point of living, from a biological perspective, is to pass on genes to the next generation by means of producing offspring. After peak maturity/adulthood, reproduction is usually no longer on the cards so ageing begins.
The place of a species in the food chain, it's environment, even it's local population plays a part in determining it's age of sexual maturity, it's age of senescence (ageing) and it's ultimate longevity. To explain how evolution has shaped many species' lifespans, here are a few examples:

- Mice have a lot of selective pressure on their shoulders - they are the perfect food for many predators - so for an individual mouse to have any chance of passing on it's genes it must sexually mature very fast before it's eaten. It takes a mouse no longer than 10 weeks to mature, and once a mate is found the gestation period for a female mouse is only around 19-21 days. After 9 months mice age and die very fast to make way for the new generation of sexually mature young.

- African Elephants are just about at the top of the food chain, by contrast. They live in herds on vast grasslands, often close to water sources. Every year each herd migrates to avoid the dry season, and the female elephant usually gives birth to just one offspring at a time, after a 20 month gestation period.
The life expectancy of an African elephant is 70 years. With no selective pressure from predators, the availability of food, and stable life in a herd, elephants have never needed to adapt to mature quickly. In fact the opposite has probably occurred. The long distance migrations over desolate savannah have caused elephants to adapt to extend their lifespan, increasing that probability of finding another herd for a suitable mate.

In terms of us, humans reside at the very top of the food chain. We are clever enough to shape our own environment which gives us a very comfortable lifestyle. Evolution is easy on us and gives us a long childhood as well as an adulthood of suitable length. Moreover, many males stay fertile even in old age to increase the chances of transferring their genes. Human life expectancy can range from 50-80 years worldwide, but could we be doing anything more to allow evolution to grant us more happy years?





In short, no. Evolution works both ways - we have a set maturation period, set peak reproductive period and a set senescence period. All set by our genes: the ultimate decider of our fate. Genes can endure in two ways: they can live in a single immortal individual or they can be passed on to another. Examples of "immortal" organisms are actually quite abundant in prokaryotic world. Some bacteria can produce spores when in environmentally unfavourable conditions, containing their own DNA. The spores are extremely resilient and can last millions of years. When environmental conditions because favourable the spore develops back into the bacterium. This method of endurance essentially cancels out any need for reproduction.

Unfortunate as some people may think, evolution has virtually decided that we're too delicate for immortality and has chosen to give us the ability to transfer our genes by reproduction. If an individual can reproduce, there comes a time where they have move aside for the next generation. Pretty philosophical.



Figures retrieved from https://www.cia.gov/library/publications/the-world-factbook/rankorder/2102rank.html

Could diabetes become curable within the next 10 years?

Image retrieved from Scientific American

In Britain today, more than 29,000 people are diagnosed with either type 1 or type 2 diabetes. 1 in 3 adults suffer from diabetic-like symptoms, including fatigue, high blood sugar and problems with vision.

Diabetes is diagnosed in every 17 out of 100,000 children yearly in England and Wales. Although the least common type as a whole, 90-95% of diabetics under 16 have Type 1 diabetes, which is normally caused by genetic factors in an individual.

Because of this, hundreds of research projects around the world are dedicated to treating, preventing and possibly curing the condition that affects the daily lives of so many people.

But how close are we to actually “curing” diabetes in humans? What research is out there, and what changes can we expect to see in the next decade?

This article aims to illustrate some of the pioneering studies in several institutions that are tackling type 1 diabetes. Before this, here is an explanation of the disease and how it affects the body:

Type 1 Diabetes Mellitus is an autoimmune disease, which means that it causes the body to attack itself. Autoantibodies – immune system components that mistakenly break down tissue in the body – attack beta cells in the pancreas. These specialised cells secrete a hormone called insulin, which acts to lower glucose levels in the bloodstream after eating or during periods of rest. The damage to the beta cells means that they cannot secrete insulin, causing dangerously high concentrations of glucose in the blood to bring about symptoms such as hyperactivity, frequent urination and increased thirst.

When all of the glucose in the blood has been used up, the body goes into panic mode because there isn’t any stored glucose around for energy. This is called hypoglycaemia, and leads to symptoms such as blurred vision, extreme tiredness and in severe cases, epileptic seizures.

Diabetes can be treated by frequent administrations of insulin to keep blood-glucose levels at bay, although this can be inconvenient and enforces a diet that has to comply with the insulin doses. The insulin has to be administrated intravenously, either through a small pump-device attached to the body or by injections. No cure is available for diabetes at this moment.

The first study in this article looks at a 3 year analysis of 33 infants in Finland, who were selected for their genetically-higher risk of developing type 1 diabetes. The researchers wanted to look at the progress of each infant as they grew up. By the age of 3 most of the children were healthy, but 4 had already developed diabetes. When analysing these children, researchers discovered a significant absence of body flora in their gastrointestinal tracts (GIT). Body flora is the “good” bacteria found in an individual’s body, and can be found on the skin, in mucous, but mostly in the GIT.

When the body floras of the diabetic children were studied, larger than normal populations of species were found that trigger inflammation of the GIT - which has been known to be a secondary symptom of diabetes as the species are thought to also attack the beta cells in the pancreas.

When looking at the healthy children, 11 of them had already started to produce autoantibodies. The researchers wanted to know why the autoantibodies hadn’t caused the disease in these children, so they came up with the idea that normal, or enhanced, levels of body flora in the body were tackling the onset of the condition in the children.

To extend on this hypothesis, a study in New York shows the bacterium Lactobacillus gasseri (found in probiotic yoghurt) can transform intestinal cells in rats to act like beta cells and secrete insulin. The bacteria possess the enzyme Glucagon-peptide 1, which is thought to bring about the intestinal cell changes. The study observed diabetic rats being fed probiotic yoghurt for 30 days, and found that at the end of the observation the rat’s had a 30% drop in glucose levels compared to healthy rats. Moreover, the diabetic rats could use their insulin-secreting intestinal cells to reduce their blood sugar levels as fast as their healthy counterparts.

This study takes the hypothesis of positive body flora modification and applies it practically. The next step in application would be to produce a bacteria-containing pill that diabetics could take daily, instead of injections.

Probably the most notable breakthrough in diabetes this decade came from a Harvard diabetes institute in October 2014. After 23 years of research initiated by the diagnosis of his son with type 1 diabetes, Dr Doug Melton and his research group managed to produce artificial, insulin-secreting beta cells from stem cells. The “beta units” were observed to secrete the hormone upon glucose-induced stimulation, resemble typical beta cells found in the pancreas genetically and structurally, and in transplantation manage to bring about a positive effect on hyperglycaemic mice.

The stem cell-derived beta cells are currently undergoing trials in other animals, but not yet primates. Because of the complexity of artificial cells we may not see beta cell transplantation in humans for at least another decade.

 A final study that deserves attention is an ongoing project at the Massachusetts Institute of Technology (MIT).  Researchers are experimenting with insulin release mechanisms by modifying the hormone itself. So far, the team at MIT have been able to change the chemical structure of insulin molecules so that it stays in the blood stream for longer, which would mean for patients that frequent injections of the hormone would not be needed. The researchers have achieved this prolonged presence of insulin by adding a hydrophobic (water-repelling) domain to the molecule. The theory behind this is that the molecule would be more likely to bind to proteins in the blood, preventing it from being broken down by sugars.

Image retrieved from Medcity News

As well as adding the domain to the molecule, a chemical group was added that binds to glucose and brings it into contact with insulin. Therefore, in high concentrations of sugar, protein-bound insulin is likely to be broken down by surrounding glucose. The combination of these two mechanisms means that insulin can not only stay in the blood for longer periods of time, but also still reduce blood-glucose levels when the blood is hyperglycaemic.

This modified insulin has already been tested on mice that are deficient in the hormone. The results showed the mice reacting more efficiently to spikes in blood-glucose concentration, compared to traditional insulin.

At this moment, further test-stages are required before this treatment can be made available on any health service, but the project is ongoing and the researchers at MIT are dedicated to produce the modified hormone in purer and safer quantities.

The field of diabetic research is a constantly progressing, and has been at an immense speed since the 1990s. Molecular biology, pharmacology and the fairly recent advanced understanding of cell biology has made all of this possible. Just by looking at the 3 studies mentioned, it’s fair to say that diabetes will become a curable disease within the next 10 years. 







Images retreived from : http://medcitynews.com/2014/04/jdrf-partners-insulin-startup-thermalin-ultra-rapid-acting-insulin-t1d/

http://www.scientificamerican.com/article/a-diabetes-cliffhanger/